OBJECTIVES: To report the effectiveness and safety of marketed biologics for RA treatment from phase 4 and observational studies, including studies with direct comparisons. METHODS: PubMed and International Pharmaceutical Abstracts (IPA) databases were searched using "arthritis, rheumatoid", combined with generic names of 10 biologics for RA (adalimumab, etanercept, anakinra, infliximab, abatacept, rituximab, golimumab, certolizumab, tocilizumab and tofacitinib) and study designs (phase 4, observational and post-market). Inclusion criteria: peer-reviewed article; published in English; phase 4 trials or observational studies on the selected drugs; reported efficacy and/or safety data.  RESULTS: Our search identified 678 articles. Thirty-six studies were included in this review after applying inclusion/exclusion criteria. Studies reported data on effectiveness (10, 28%), safety (9, 25%) or both (17, 47%). The sample size varied from 27 to 34947 (median=1439). Overall, biologics displayed improved effectiveness compared to traditional disease-modifying anti-rheumatic drugs (tDMARDs). Eleven (31%) studies reported effectiveness from direct comparisons. Three studies found a better effectiveness among tumor necrosis factor inhibitors (TNFi) users versus tDMARDs users. Two studies claimed that switching to rituximab rather than to an alternative TNFi would be a better choice for patients who had previously failed TNFi. Three studies concluded that biologics had a worse safety profile than tDMARDs from direct comparisons. Adverse events (AEs) rates varied from 12.5% for adalimumab to 43% for infliximab, and serious adverse events (SAEs) rates varied from 4.7% for abatacept to 10% for infliximab. Common AEs included injection site reaction, arthralgia, headache, and rash. Common SAEs included infections and malignancy. CONCLUSIONS: The review demonstrates that biologics are excellent therapeutic options for RA patients but safety outcomes were highly variable, depending upon the study design and biologic evaluated. Therefore, direct comparisons of both intra-class and inter-class biologics are needed to adequately compare safety and effectiveness profiles.